Is serum-derived exosomal hTERT transcript a marker of oncogenic activity in primary brain tumors? An exploratory study

Orit Uziel*, Andrew A. Kanner, Einat Beery, Sapir Lev, Meir Lahav, Suzana Horn-Fichman, Sagi Har Nof, Yuseph Laviv, S. Yust-Katz, Alexandra Amiel, Ramez Abu Shkara, Mustafa Siddeeq, Adva Levy-Barda, Pia Raanani, Yaron Sela, Zvi Cohen, Tali Siegal

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In order to proliferate indefinitely, all tumors require a telomere maintenance mechanism. The expression of human telomerase reverse transcriptase (hTERT) enables telomere maintenance and provides cancer cells with limitless replicative potential. As such, it may serve as an attractive biomarker for oncogenic activity. This study explored whether a liquid biopsy that analyses blood derived exosomal hTERT transcript (e-hTERT-trans) may serve as such a biomarker in gliomas and meningiomas when compared to healthy controls. Methods: Exosomes were isolated from the pre-operative sera of patients' samples stored in the biobank of both Rabin and Sheba Medical Centers. The levels of e-hTERT-trans were measured in 81 healthy controls, 117 meningiomas, 17 low-grade gliomas, and 61 glioblastomas. Clinical parameters of the patients were collected retrospectively and compared to the levels of the e-hTERT-trans. Results: The upper normal limit of controls e-hTERT-trans was 1.85 relative quantitation (RQ). The rate of detection increased with rising tumor grade and correlated with tumor recurrence in meningiomas: mean RQ without recurrence (2.17 ± 11.7) versus with recurrence (3.59 ± 4.42; p = 0.002). In glioblastomas, preoperative measurements correlated with tumor volume and with the disease course on serial sampling. Conclusions: We demonstrated for the first time that the expression of e-hTERT-trans transcript can be measured in the serum of primary brain tumors. This exosomal marker carries the potential to serve as a biomarker once used in conjunction with other clinical and radiological parameters. Future studies are required to investigate whether the sensitivity could be augmented and whether it can be implemented into routine patients care.

Original languageEnglish
Article numbere6784
JournalCancer Medicine
Volume13
Issue number1
DOIs
StatePublished - Jan 2024

Funding

FundersFunder number
Mary Bendet Foundation

    Keywords

    • atypical meningioma
    • exosomes
    • glioblastoma
    • liquid biopsy
    • meningioma
    • telomerase

    Fingerprint

    Dive into the research topics of 'Is serum-derived exosomal hTERT transcript a marker of oncogenic activity in primary brain tumors? An exploratory study'. Together they form a unique fingerprint.

    Cite this